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Exercise Redox Signalling
Published in James N. Cobley, Gareth W. Davison, Oxidative Eustress in Exercise Physiology, 2022
Ruy A. Louzada, Jessica Bouviere, Rodrigo S. Fortunato, Denise P. Carvalho
In addition, phosphatase and tensin homolog (PTEN) and protein phosphatase 2A (PP2A) control two crucial steps in PI3K/Akt signalling, and they can be targeted by ROS-mediated signalling (Figure 3.3). Besides the transitory inhibition of PTEN (Lee et al., 2002), ROS-mediated signalling causes phosphorylation of PTEN, triggering its degradation (Abraham and O’Neill, 2014). For PP2A, it has been demonstrated that peroxynitrite-mediated nitration resulted in inhibition of PP2A, which promotes sustained activation of PI3/Akt signalling (Low et al., 2014). Additionally, Akt alone is also a redox-sensitive protein that has a disulphide bond between Cys297 and Cys311 (Murata et al., 2003) and other two cysteine residues in the pleckstrin homology domain (Cys60 and Cys77). Thus, the net balance toward PI3K/Akt/mTORC pathways might be caused by a pro-oxidant environment after exercise and thereby sustaining the activation of an anabolic cascade to mediate hypertrophy (Figure 3.3).
Role of Oxidative Stress in the Onset of Alzheimer’s Disease
Published in Abhai Kumar, Debasis Bagchi, Antioxidants and Functional Foods for Neurodegenerative Disorders, 2021
Tasnuva Sarowar, Md. Hafiz Uddin
The tau protein in neurofibrillary tangles become hyperphosphorylated which changes the conformation of tau helices, leading to disruption in tau-microtubule association. Eventually, this leads to loss of necessary cellular function and cell death (Iqbal et al. 1998). Hyperphosphorylated tau is not only found in AD brains but also in a number of other neurodegenerative diseases, such as corticobasal degeneration, frontotemporal dementia, and Niemann pick disease (Wang, Wang, and Tian 2014). The phosphorylation of tau protein can be mediated by several kinases and phosphatases, such as glycogen synthase kinase 3 beta (GSK3β), cyclin-dependent kinase (CDK5), and extracellular signal-related kinases. The phosphorylation via GSK3β can be reversed by protein phosphatase 2A (PP2A). Thus, activation of GSK3β and inhibition of PP2A can lead to a vicious cycle. Due to hyperphosphorylation, tau can form paired helical form aggregates that disrupt the microtubule dynamics (Avila et al. 2004).
Synapses
Published in Nassir H. Sabah, Neuromuscular Fundamentals, 2020
The phosphate group is hydrolyzed back to an OH– group by enzymes referred to as phosphatases, and the process is known as dephosphorylation. Protein phosphatase 1 (PP1) dephosphorylates a variety of proteins as well as K+ and Ca2+ channels, NMDA, and AMPA glutamate receptors. Protein phosphatase 2A (PP2A) also dephosphorylates a range of proteins that overlap with those of PP1, in addition to tau protein that stabilizes microtubules of the cytoskeleton. Excessive phosphorylation of tau protein is associated with Alzheimer’s disease. Protein phosphatase 2B (PP2B), also known as calcineurin, is abundant in neurons and is activated by Ca2+. It activates T cells of the immune system and dephosphorylates AMPA receptors. Protein phosphorylation and dephosphorylation are of fundamental importance in cell functioning as it is the major molecular mechanism through which protein activity in a cell is regulated both in and outside the nervous system.
The Expression and Role of microRNA-133a in Plasma of Patients with Kawasaki Disease
Published in Immunological Investigations, 2022
Yeping Luo, Meng Yu, Pengzhu Li, Lihua Huang, Jiping Wu, Min Kong, Ying Li, Zhixiang Wu, Zhijuan Kang, Lu Yi, Zuocheng Yang
PPP2CA is the catalytic submit of protein phosphatase 2A (PP2A). PP2A is the main serine/threonine phosphatase in organism which control dephosphorylation of thousands of phosphoprotein substrates(Kolupaeva 2019; Shi 2009). The dephosphorylation of PP2A is associated with regulating the interity and permeability of vascular endothelial by influencing adhesion connection, tight connection, and the coordination of cytoskeletal components (Le Guelte et al. 2012; Tar et al. 2006). PPP2A also involves in wnt signaling pathway and maintains the stability of VE-cadherin-catenin complex that can prevent the increase of vascular endothelial permeability (Giannotta et al. 2013; Rho et al. 2017; Schulte et al. 2011). Phosphorylation of catenin at Tyr will prevent their interaction and lead to the cleavage of the complex’s extracellular domain which can be detected after dissociation in blood called sVE-cadherin (Kasa et al. 2013; Vilgrain et al. 2013).
Overexpression of cancerous inhibitor ofPP2A (CIP2A) in acute myeloid leukemia
Published in Expert Review of Hematology, 2022
Reem Hasanin, Ghada Mossallam, Sally Elfishawi, Ahmed Rabea, Nayera Hamdy
Protein phosphatase 2A (PP2A) is a major serine/threonine phosphatase and tumor suppressor that negatively regulates numerous signal transduction pathways involved in cell proliferation, differentiation, and survival [5]. PP2A inhibition is a common event in AML [6]. Restoration of PP2A activity induces cell growth arrest and caspase-dependent apoptosis suggesting that PP2A inactivation plays a crucial role in AML and its activation represents a potential novel therapeutic target [6,7]. Cancerous inhibitor of PP2A (CIP2A) is identified as an endogenous inhibitor of PP2A. It inhibits PP2A-mediated dephosphorylation of the oncogene kinase c-MYC in human malignancies [7]. CIP2A is overexpressed in several human malignancies, including hematologic malignancies, especially in newly diagnosed AML patients and at relapse [8,9]. CIP2A overexpression was shown to be a recurrent event in cytogenetic normal AML patients with a poor prognostic impact on the overall survival and was also associated with disease progression to blast crisis in chronic myeloid leukemia (CML) [9,10].
Blocking protein phosphatase 2A with a peptide protects mice against bleomycin-induced pulmonary fibrosis
Published in Experimental Lung Research, 2020
It has been reported that the vast majority of biological processes, including EndMT, are regulated by the balance between the activities of kinases and phosphatases.16 Protein phosphatase 2 A (PP2A) is a ubiquitously expressed protein serine/threonine phosphatase that accounts for a large fraction of the phosphatase activity in eukaryotic cells.17 As a heterotrimer, PP2A is composed of three subunits: a structural subunit (PP2Aa), a regulatory B-type subunit (PP2Ab) and a catalytic C subunit (PP2Ac).18 Our previous study suggested that tyrosine 127 nitration in the catalytic subunit of PP2Ac is associated with EndMT via tight junction disassembly in renal interstitial fibrosis. Furthermore, inhibiting Tyr127 nitration with a novel mimic peptide derived from PP2Ac conjugation of a cell penetrating peptide (CPP: TAT), termed TAT-Y127WT, can prevent endothelial cells from undergoing EndMT in renal interstitial fibrosis.19